The goal of this research is to investigate Hodgkin's disease (HD) by means of long-term tissue cultures derived from the tumor. We have found a tumor antigen in HD cultures that is not demonstrable in noncultured tumor cells and is present in small amounts in normal cultured cells. The HD culture antigen is on the cell surface by immunofluorescence and isotopic antibody techniques, and in the supernatant medium by density gradient sedimentation, gel diffusion, electrophoresis, and column chromatography. The HD tissue culture antigen may be a normal cellular constituent, a tumor-specific antigen, or a component of an oncogenic virus. Replication of cells in culture is required for the expression of the antigen. Based on these data we are now prepared to determine the pathogenetic significance of the HD culture antigen. Crucial to this goal is to define the relationship of the cells that replicate in HD monolayer cultures to the neoplastic cell in vivo. We propose to purify the antigen by sensitive analytic methods and to develop means to assay trace amounts of the antigen by radioimmune precipitation. Additional studies of the apparent absence of the antigen in noncultured cells are required. Since the antigen is on the cell surface, the surface proteins of cultured cells will be iodinated enzymatically and fractionated by analytic methods. The possibility of cross reactivity of the HD antigen to known oncogenic viruses will be pursued. Finally, autoaggressive cell-mediated immune reactivity will be investigated by lymphocyte cytotoxicity assays with autologous cells from HD cultures.